Annexon Outlines Registrational Program For ANX007 in GA with FDA Alignment On Vision Preservation As Primary Endpoint

Annexon outlined its global registrational program for ANX007, a first-in-class C1q and classical complement inhibitor, for the treatment of patients with geographic atrophy (GA). 

Annexon has gained alignment with the FDA on a phase 3 registration program that includes using, for the first-time, the prevention of ≥15-letter loss of best corrected visual acuity (BCVA) as the primary outcome measure, as well as conducting a comparison of ANX007 to an injection agent, consistent with requests for trials across ophthalmic indications. Notably, the FDA has not required Annexon to study the slowing of lesion growth as measured by fundus autofluorescence (FAF), an anatomical endpoint used for the approval of other GA programs.

“We are thrilled to have aligned with FDA on vision preservation as the primary endpoint in our phase 3 GA program, based on the statistically significant and dose-dependent visual protection ANX007 demonstrated in the phase 2 ARCHER trial,” Douglas Love, chief executive officer of Annexon, said in a company news release. “Blocking C1q with ANX007 is designed to stop classical complement inflammation that drives photoreceptor damage and vision loss. Considering the robust preservation of vision demonstrated by ANX007 in the ARCHER trial, and that current FDA-approved treatments have not shown a meaningful functional benefit after years of treatment, we are encouraged by the potential for ANX007 to demonstrate significant protection against vision loss as measured by BCVA ≥15-letter loss in a head-to-head study. We are excited to embark on this global pivotal program with the aim of providing meaningful functional benefit and offering a new transformative treatment to the patients, and their families, affected by GA.” 

Annexon’s registration program will initiate first with ARCHER II, a global sham-controlled trial designed to confirm the results from the phase 2 ARCHER trial, and potentially expedite the path to regulatory approval in Europe, where there are approximately 2.5 million people living with GA. Given the availability of FDA-approved treatments in the US, Annexon plans to conduct its injection-controlled head-to-head study, ARROW, against Syfovre (pegcetacoplan injection), with the potential to underscore ANX007’s unique mechanism of action and critical differentiation on visual function. ARCHER II is expected to begin enrollment in mid-2024, followed by ARROW in late 2024.

“For the millions of patients living with GA, loss of sight is coupled with the loss of independence, leaving a significant impact on quality of life,” Jeffrey S. Heier, MD, director of the Retina Service and Retina Research, Ophthalmic Consultants of Boston, and an investigator in ARCHER, said in a company news release. “It is every physician’s goal to preserve vision for as long as possible. Based on the outcome of the ARCHER trial, I am excited by the potential of ANX007 and its distinct neuroprotective mechanism of action, and I look forward to further understanding its role in the treatment of GA through its robust phase 3 program.” 

ANX007 Global GA Registrational Program Overview

• ARCHER II Global Sham-Controlled Trial: The phase 3 ARCHER II trial is designed to enroll approximately 400 patients with GA secondary to age-related macular degeneration (AMD) who will be randomized 1:1 to receive a monthly dose of ANX007 or sham procedure. The primary endpoint will be the prevention of ≥15-letter loss of best corrected visual acuity (BCVA), in patients assessed through 12 months. BCVA ≥15-letter loss is a well-established functional endpoint that has served as the basis for numerous ophthalmology drug approvals by the FDA and EMA. Key secondary endpoints in ARCHER II include safety, low-luminance visual acuity (LLVA), and low-luminance visual deficit (LLVD).
• ARROW Head-to-Head Trial: The phase 3 ARROW trial is designed to enroll approximately 500 patients with GA to evaluate a monthly dose of ANX007 versus Syfovre as an injection comparator, an FDA-approved drug shown to slow lesion growth. The primary endpoint will be the prevention of ≥15-letter loss of BCVA assessed through 12 months and is designed to differentiate vision protection from slowing of lesion growth, offering patients a functional benefit alternative.

Annexon continues to engage with the European Medicines Agency following receipt of PRIME designation and will seek feedback from EMA on the pivotal phase 3 program in the first half of 2024. ANX007 is the first therapeutic candidate for the treatment of GA to receive PRIME designation, which provides early and proactive support to developers of promising medicines that may offer a major therapeutic advantage over existing treatments or benefit to patients without treatment options.